Type D simian retroviruses (SRVs) continue to endemically infect Macaca fuscata, Macaca mulatta, and Macaca nigra at the ORPRC. Four distinct SRVs representing three serologic groups are present in one or more species. Closely related variants of these SRVs are also present. A direct cause and effect relationship between type D SRVs and simian immunodeficiency syndrome (SAIDS) is almost certain. Expression of disease (or lack of) is likely dependent on the infecting variant of SRV and species. The mechanism(s) leading to immunodeficiency are largely unknown. Continuation of proposed surveillance and management programs will likely result in the establishment of type D SRV-free macaque colonies. Studies are proposed to characterize synthetic SRV-2 envelope peptides, cellular tropism of SRVs, and the molecular differences in the envelope region of variant viruses, with different disease expression. The focus is to characterize the virus-host cell interactions that determine which cells in the host are targeted by type D SRVs as a step in defining mechanisms responsible for immunosuppression.